The peroxisome proliferator-activated receptors (PPARs) are transcription factors known to play a central role in regulating the storage and catabolism of dietary fats and are also known as lipid sensors of the body. There are three PPAR subtypes: PPARα, PPARγ, and PPARδ. As with other members of the nuclear receptor gene family, the PPARs are ligand-activated transcription factors. Agonist activation of the receptor results in changes in the expression level of mRNAs encoded by PPAR target genes.

The use of PPARγ activators, e.g. rosiglitazone and pioglitazone (glitazones or TZDs), in the treatment of type 2 diabetes has been established due to their ability to lower blood glucose and insulin levels and improve insulin sensitivity. Similarly, PPARα activators, e.g. fenofibrate and clofibrate (fibrates), have been used for more than three decades for their ability to lower plasma triglycerides (TG) and moderately raise HDL-cholesterol.

Currently no marketed drug is available which targets the PPARδ receptor, but several compounds are in exploratory stages providing data that PPARδ is involved in lipid homeostasis.

HPP 593 is a novel, potent orally active, selective PPAR delta agonist A two-week, placebo controlled, dose escalation study in obese, healthy normal subjects is ongoing, measuring lipids( LDL, HDL, TG, FFA, and postprandial lipid test), glucose (fasting glucose, insulin and postprandial glucose challenge test), weight, liver fat content and biomarkers for inflammation and oxidative stress.

HPP 593 has the potential to demonstrate: additive LDL lowering effect to statin-treatment; ability to treat dyslipidemia not properly treated with statins, i.e. low HDL, high TG (25 -40% of patients with cardiovascular disease); additional beneficial effect on cardiovascular risk factors such as, obesity, insulin resistance, oxidative stress, hypertension and has the potential for beneficial effect on muscle and bone density.